Abstract
PEGylation is one of the most commonly applied approaches to realize the stealthiness of the conjugated nanomaterials in the systemic circulation. Nevertheless, despite the fact that Polyethylene glycol (PEG) is biologically inert, a mounting body of evidences has confirmed the presence of anti-PEG antibodies (anti-PEG Abs) that trigger an immunogenic response against PEG conjugates in a manner wherein PEG acts as a hapten. Since anti-PEG Abs are correlated with the accelerated clearance of subsequently administered doses of PEGylated nanocarriers, via a phenomenon known as "accelerated blood clearance" phenomenon, the existence of anti-PEG Abs has been claimed for the reduced efficiency of PEGylated therapeutics and/or development of severe adverse effects. Accordingly, careful monitoring for anti-PEG Abs is necessary prior to and throughout a course of treatment with PEGylated therapeutics. Furthermore, strategies to avert the challenges of PEG-specific immunity are needed with a deeper understanding of the mechanism of anti-PEG immunity.